Past efforts have focused on developing a well-characterized cohort of patients for longitudinal studies of the dementia syndrome of Huntington's disease (HD). To that end, groups of 80 HD patients and 22 control subjects have been recruited. In the next five years, the patient sample will be augmented with patients of early and late onset age Clinical Core. We will follow that cohort of 150 patients and 40 gene-negative controls in our Longitudinal Core Study to characterize, for the first time, the natural history of dementia in HD. This study is a collaborative effort between this Project. Neuroimaging Project and the Clinical Core. The cognitive data from this longitudinal study will be analyzed in conjunction with the annual assessments of disease severity as indexed by clinical measures (neuroimaging) obtained biannually on the same patients. The pattern and rate of cognitive decline will be examined, and the relative contributions of severity and rate of striatal and cortical atrophy, CAG repeat length (CoreD), and onset age to differences in rates of decline will be determined. The delineation of the natural history of dementia in HD will be helpful to clinicians in managing patient care, and will be particularly relevant for future clinical trials of potential therapeutic agents. Voluntary motor impairment is prominent in HD, but has not been examined extensively. Severity of impairment appears to vary across patients and across motor tasks. Voluntary motor performance will be assessed in mildly to moderately affected patients using the motor impairment scale from the Quantitated Neurological Exam, a limb apraxia battery, motor learning tasks, and tasks assessing the timing programming and sequencing of motor actions. Motor task performance will be related to cortical and subcortical atrophy to determine the anatomical correlates of impaired voluntary movement in HD, and to the Huntington's Disease Activities of Daily Living Scale to assess the impact of voluntary motor impairment on functional abilities. These studies will delineate those aspects of voluntary motor performance most affected in HD and lead to a better understanding of the anatomical correlates of voluntary motor activity in general.